As an extension of our GVH work, my laboratory has recently begun to investigate the effects of CSA on peripheral T cell immune function, as well as on the ability of CSA-treated mice to develop functional T cells from bone marrow stem cells. Multiple injections of different doses of CSA (30 or 75 mg/kg) had different effects on peripheral T cell function. The lower dose of CSA selectively abrogated CD4 T helper cell function, but not CD8 T helper or effector function. Suppressor cells were detected that suppressed the CD4 but not CD8 T cell function of normal mice. Seventy-five mg/kg abolished all T cell function tested, and suppressor cells were detected which had a similar effect on T cells from normal mice. Mice treated with these doses of CSA were unable to develop CD4 T helper cell function from normal stem cells, and this defect was due to CSA-induced thymic damage. These results indicate that abrogation of T cell function by CSA can be selective, depending on the dose of CSA administered. This study also suggests that in vitro CD4 and CD8 T cell functional analysis should be performed in human allograft recipients undergoing CSA treatment, and raises the possibility that not all human T cell functional pathways will be abrogated by a particular CSA protocol in allograft patients. Recent in vitro data suggest that distinct functional T cell subsets of human PBL will be differentially susceptible to CSA.